In the late 1970s, dynamic light scattering theory was applied to living tissue to measure blood flow. Multiple scattering from the blood occurred, resulting for example, in a Doppler broadening of the indirect laser linewidth. In the early 1980s, a theory for how to use diffuse light to measure motional fluctuations in turbid media was discovered. The theory was termed “diffusing wave spectroscopy.”
Diffusing wave spectroscopy enabled a range of dynamical studies of optically dense systems in which scattering particles are moving. However, in these systems, the medium generally was homogeneous in that there were no spatial variations in the dynamic or optical properties. Therefore, these techniques for measuring motions with diffuse light were limited because they could not characterize media with spatially varying, dynamic properties.
Overtime diffuse imaging and spectroscopy techniques evolved to permit measurement and imaging heterogeneous media such as tissue. The method could be applied to tumors, burns, and other real world structures found in the human body. Such techniques are discussed in detail in U.S. Pat. No. 6,076,010, which is herein incorporated by reference in its entirety. Specifically, these techniques irradiate the medium with a source of light that diffuses through the medium. A measurement is taken of the temporal intensity fluctuations of photon streams that have been scattered within the medium. The medium's properties, for example blood flow rate, are then determined using measured temporal correlation functions of the diffuse light (for example as a function of placement on the tissue surface). We will refer to the methodology as diffuse correlation spectroscopy (DCS).
Various other methods for measuring blood flow have been developed and employed. For example, conventional venous occlusion plethysmography has been employed for more than fifty years in muscle perfusion investigations. However, this method does not provide regional information and can be used only in the static state, during functional activation, or during brief exercise because it interrupts blood flow. Also, ultrasound Doppler techniques are a common clinical tool used to measure blood flow in large vessels. However, the Doppler techniques are not very sensitive to blood flow in smaller vessels, and do not readily permit continuous measurements during exercise. Laser Doppler techniques also have been used more recently, but typically they only measure the tissue surface. Magnetic resonance imaging (MRI) has high temporal and spatial resolution, and has become a gold standard technique for noninvasive measurement of blood flow and metabolic response. However, MRI's clinical use is limited due to high cost and poor mobility, and it's function form has poor sensitivity.
Diffuse correlation spectroscopy (DCS) is an emerging technique for continuous measurement of relative blood flow non-invasively in deep tissues. It has been successfully applied in studies of brain hemodynamics, PDT dosimetry and for measurement of burn depth. DCS enables measurements of relative blood flow (rBF) with high temporal and low spatial resolution in tissue. To date most (but not all) applications of DCS have been in small animal studies wherein source-detector separations were comparatively small. Discussion of DCS techniques has been described in U.S. Pat. No. 6,076,010, which is incorporated herein by reference in its entirety.
Combining these blood flow rate determinations with oxygenation and hemodynamic tissue properties determined by diffused optical spectroscopy or characteristics further facilitates the understanding of vascular conditions and tissue metabolism, as well as for example in peripheral arterial disease (PAD). In general these improved measurements will enable improved screening of tissues and treatment assessment, as well as to improved fundamental understanding of tissue function. Therefore, there is a real value in such non-invasive optical techniques for study of blood flow, hemodynamics and oxygenation in tissue.